chr6-29829862-C-T

Variant names:

• chr6-29829862-C-T
• rs1049033
• NM_001384290.1:c.942C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001384290.1(HLA-G):​c.942C>T​(p.Gly314Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,612,362 control chromosomes in the GnomAD database, including 69,845 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.27 (5526 hom., cov: 31)
  • Exomes 𝑓: 0.29 (64319 hom.)
• Consequence: HLA-G NM_001384290.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 22 publications found

Genes affected

HLA-G (HGNC:4964): (major histocompatibility complex, class I, G) HLA-G belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. HLA-G is expressed on fetal derived placental cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domain, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exon 6 encodes the cytoplasmic tail. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384290.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	NM_001384290.1	MANE Select	c.942C>T	p.Gly314Gly	synonymous	Exon 5 of 7	NP_001371219.1
	HLA-G	NM_001363567.2		c.957C>T	p.Gly319Gly	synonymous	Exon 6 of 8	NP_001350496.1
	HLA-G	NM_001384280.1		c.957C>T	p.Gly319Gly	synonymous	Exon 7 of 9	NP_001371209.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	ENST00000360323.11	TSL:6 MANE Select	c.942C>T	p.Gly314Gly	synonymous	Exon 5 of 7	ENSP00000353472.6
	HLA-G	ENST00000376828.6	TSL:6	c.957C>T	p.Gly319Gly	synonymous	Exon 6 of 8	ENSP00000366024.2
	HLA-G	ENST00000376818.7	TSL:6	c.666C>T	p.Gly222Gly	synonymous	Exon 4 of 6	ENSP00000366014.3

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40607 AN: 151902 Hom.: 5524 Cov.: 31

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.273

GnomAD2 exomes AF: 0.266 AC: 66809 AN: 251054 AF XY: 0.270

Gnomad AFR exome AF: 0.255

Gnomad AMR exome AF: 0.271

Gnomad ASJ exome AF: 0.386

Gnomad EAS exome AF: 0.0873

Gnomad FIN exome AF: 0.194

Gnomad NFE exome AF: 0.288

Gnomad OTH exome AF: 0.273

GnomAD4 exome AF: 0.292 AC: 426842 AN: 1460342 Hom.: 64319 Cov.: 40 AF XY: 0.294 AC XY: 213427 AN XY: 726584

African (AFR) AF: 0.256 AC: 8553 AN: 33450

American (AMR) AF: 0.274 AC: 12220 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 10013 AN: 26108

East Asian (EAS) AF: 0.151 AC: 5997 AN: 39690

South Asian (SAS) AF: 0.303 AC: 26089 AN: 86202

European-Finnish (FIN) AF: 0.203 AC: 10851 AN: 53412

Middle Eastern (MID) AF: 0.304 AC: 1754 AN: 5762

European-Non Finnish (NFE) AF: 0.300 AC: 333734 AN: 1110702

Other (OTH) AF: 0.292 AC: 17631 AN: 60344

GnomAD4 genome AF: 0.267 AC: 40630 AN: 152020 Hom.: 5526 Cov.: 31 AF XY: 0.263 AC XY: 19547 AN XY: 74338

African (AFR) AF: 0.257 AC: 10651 AN: 41428

American (AMR) AF: 0.276 AC: 4215 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1327 AN: 3470

East Asian (EAS) AF: 0.109 AC: 561 AN: 5162

South Asian (SAS) AF: 0.265 AC: 1279 AN: 4818

European-Finnish (FIN) AF: 0.193 AC: 2040 AN: 10582

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.290 AC: 19705 AN: 67972

Other (OTH) AF: 0.269 AC: 567 AN: 2108

Alfa AF: 0.289 Hom.: 3933

Bravo AF: 0.273

Asia WGS AF: 0.178 AC: 625 AN: 3478

EpiCase AF: 0.308

EpiControl AF: 0.294

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	11
DANN	Benign	0.54
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.26		Position offset: 17

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1049033; hg19: chr6-29797639; COSMIC: COSV64405869; COSMIC: COSV64405869;